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Letters in Drug Design & Discovery

Editor-in-Chief

ISSN (Print): 1570-1808
ISSN (Online): 1875-628X

Research Article

Mechanism of American Ginseng Against Type 2 Diabetes Mellitus Based on Network Pharmacology & Molecular Docking

Author(s): Jiaxin Li, Siqi Chen, Bo Wang, Jiaming Xie, Xinyu Wu, Xinying Hu, Jing Liu, Yi Zhang, Junzhi Wang* and Pengling Ge*

Volume 21, Issue 11, 2024

Published on: 26 June, 2023

Page: [2046 - 2062] Pages: 17

DOI: 10.2174/1570180820666230518095837

Price: $65

Abstract

Background: Ginseng is one of the top-selling natural products worldwide and has been shown to have significant effects. Nonetheless, there is limited research on American ginseng when compared to Asian ginseng. A small number of studies have demonstrated the therapeutic benefits of American ginseng, which include antioxidant, anti-inflammatory, and immune-stimulating activities.

Objective: The objective of our research is to predict the molecular mechanism by which American ginseng combats Type 2 diabetes mellitus (T2DM) using Network Pharmacology and Molecular Docking techniques. By doing so, we aim to reveal one of the comprehensive mechanisms through which American ginseng exerts its therapeutic effects.

Methods: We conducted a search for related compounds in American ginseng using the TCMSP database, which we then utilized to classify potential targets for the major ingredients. We obtained targets associated with T2DM from various databases, including PharmGKB, OMIM, TTD, GeneCards, and DrugBank. Using STRING and Cytoscape software, we constructed PPI networks. We subsequently performed GO and KEGG analysis on the targets using the R programming language. Ligand and target structures were acquired from PubChem and PDB databases, respectively. Chem3D and AutoDock software was used to process the structures, while PyMoL was employed for molecular docking analysis.

Results: Several investigations have indicated that PTGS2, NFKBIA, PRKCA, IL1B, NCOA2, and LPL targets are significantly associated with American ginseng's effectiveness in treating T2DM. Molecular docking analysis further validated these findings. We discovered three active components with highaffinity, namely papaverine, ginsenoside-rh2, and beta-sitosterol.

Conclusion: The outcomes of our predictions could contribute to the development of American ginseng or its active constituents as an alternative therapy for T2DM.

[1]
IDF Diabetes Atlas 10th edition. Available from: https://diabetesatlas.org/
[2]
Yin, B.; Bi, Y.M.; Fan, G.J.; Xia, Y.Q. Molecular mechanism of the effect of huanglian jiedu decoction on type 2 diabetes mellitus based on network pharmacology and molecular docking. J. Diabetes Res., 2020, 2020, 5273914.
[http://dx.doi.org/10.1155/2020/5273914] [PMID: 33134394]
[3]
Chatterjee, S.; Khunti, K.; Davies, M.J. Type 2 diabetes. Lancet, 2017, 389(10085), 2239-2251.
[http://dx.doi.org/10.1016/S0140-6736(17)30058-2] [PMID: 28190580]
[4]
Szczuka, D.; Nowak, A.; Zakłos-Szyda, M.; Kochan, E.; Szymańska, G.; Motyl, I.; Blasiak, J. American ginseng (Panax quinquefolium L.) as a source of bioactive phytochemicals with pro-health properties. Nutrients, 2019, 11(5), 1041.
[http://dx.doi.org/10.3390/nu11051041] [PMID: 31075951]
[5]
Wang, L.; Huang, Y.; Yin, G.; Wang, J.; Wang, P.; Chen, Z.Y.; Wang, T.; Ren, G. Antimicrobial activities of Asian ginseng, American ginseng, and notoginseng. Phytother. Res., 2020, 34(6), 1226-1236.
[http://dx.doi.org/10.1002/ptr.6605] [PMID: 31885119]
[6]
Kan, J.; Velliquette, R.A.; Grann, K.; Burns, C.R.; Scholten, J.; Tian, F.; Zhang, Q.; Gui, M. A novel botanical formula prevents diabetes by improving insulin resistance. BMC Complement. Altern. Med., 2017, 17(1), 352.
[http://dx.doi.org/10.1186/s12906-017-1848-3] [PMID: 28679380]
[7]
Wu, Q.; Hu, Y. Systematic evaluation of the mechanisms of Mulberry leaf (Morus alba Linne) acting on diabetes based on network pharmacology and molecular docking. Comb. Chem. High Throughput Screen., 2021, 24(5), 668-682.
[http://dx.doi.org/10.2174/1386207323666200914103719] [PMID: 32928080]
[8]
Hopkins, A.L. Network pharmacology. Nat. Biotechnol., 2007, 25(10), 1110-1111.
[http://dx.doi.org/10.1038/nbt1007-1110] [PMID: 17921993]
[9]
Li, Z.H.; Yu, D.; Huang, N.N.; Wu, J.K.; Du, X.W.; Wang, X.J. Immunoregulatory mechanism studies of ginseng leaves on lung cancer based on network pharmacology and molecular docking. Sci. Rep., 2021, 11(1), 18201.
[http://dx.doi.org/10.1038/s41598-021-97115-8] [PMID: 34521875]
[10]
Zhang, R.; Zhu, X.; Bai, H.; Ning, K. Network pharmacology databases for traditional Chinese medicine: Review and assessment. Front. Pharmacol., 2019, 10, 123.
[http://dx.doi.org/10.3389/fphar.2019.00123] [PMID: 30846939]
[11]
Zhou, Z.; Chen, B.; Chen, S.; Lin, M.; Chen, Y.; Jin, S.; Chen, W.; Zhang, Y. Applications of network pharmacology in traditional Chinese medicine research. Evid. Based Complement. Alternat. Med., 2020, 2020, 1646905.
[http://dx.doi.org/10.1155/2020/1646905] [PMID: 32148533]
[12]
Zhang, Q.; Li, R.; Peng, W.; Zhang, M.; Liu, J.; Wei, S.; Wang, J.; Wu, C.; Gao, Y.; Pu, X. Identification of the active constituents and significant pathways of Guizhi-Shaoyao-Zhimu decoction for the treatment of diabetes mellitus based on molecular docking and network pharmacology. Comb. Chem. High Throughput Screen., 2020, 22(9), 584-598.
[http://dx.doi.org/10.2174/1386207322666191022101613] [PMID: 31642770]
[13]
Guo, W.; Huang, J.; Wang, N.; Tan, H.Y.; Cheung, F.; Chen, F.; Feng, Y. Integrating network pharmacology and pharmacological evaluation for deciphering the action mechanism of herbal formula zuojin pill in suppressing hepatocellular carcinoma. Front. Pharmacol., 2019, 10, 1185.
[http://dx.doi.org/10.3389/fphar.2019.01185] [PMID: 31649545]
[14]
Lin, Y.; Shen, C.; Wang, F.; Fang, Z.; Shen, G. Network pharmacology and molecular docking study on the potential mechanism of Yi-Qi-Huo-Xue-Tong-Luo formula in treating diabetic peripheral neuropathy. J. Diabetes Res., 2021, 2021, 9941791.
[http://dx.doi.org/10.1155/2021/9941791] [PMID: 34159207]
[15]
Mering, C.; Huynen, M.; Jaeggi, D.; Schmidt, S.; Bork, P.; Snel, B. STRING: A database of predicted functional associations between proteins. Nucleic Acids Res., 2003, 31(1), 258-261.
[http://dx.doi.org/10.1093/nar/gkg034] [PMID: 12519996]
[16]
Chu, M.; Gao, T.; Zhang, X.; Kang, W.; Feng, Y.; Cai, Z.; Wu, P. Elucidation of potential targets of san-miao-san in the treatment of osteoarthritis based on network pharmacology and molecular docking analysis. Evid. Based Complement. Alternat. Med., 2022, 2022, 7663212.
[http://dx.doi.org/10.1155/2022/7663212] [PMID: 35087596]
[17]
Huang, J.; Teh, B.M.; Xu, Z.; Yuan, Z.; Zhou, C.; Shi, Y.; Shen, Y. The possible mechanism of Hippophae fructus oil applied in tympanic membrane repair identified based on network pharmacology and molecular docking. J. Clin. Lab. Anal., 2022, 36(1), e24157.
[http://dx.doi.org/10.1002/jcla.24157] [PMID: 34859918]
[18]
Zhang, X.; Shen, T.; Zhou, X.; Tang, X.; Gao, R.; Xu, L.; Wang, L.; Zhou, Z.; Lin, J.; Hu, Y. Network pharmacology based virtual screening of active constituents of Prunella vulgaris L. and the molecular mechanism against breast cancer. Sci. Rep., 2020, 10(1), 15730.
[http://dx.doi.org/10.1038/s41598-020-72797-8] [PMID: 32978480]
[19]
Zhang, J.; Liu, X.; Zhou, W.; Cheng, G.; Wu, J.; Guo, S.; Jia, S.; Liu, Y.; Li, B.; Zhang, X.; Wang, M. A bioinformatics investigation into molecular mechanism of Yinzhihuang granules for treating hepatitis B by network pharmacology and molecular docking verification. Sci. Rep., 2020, 10(1), 11448.
[http://dx.doi.org/10.1038/s41598-020-68224-7] [PMID: 32651427]
[20]
Song, X.; Zhang, Y.; Dai, E.; Wang, L.; Du, H. Prediction of triptolide targets in rheumatoid arthritis using network pharmacology and molecular docking. Int. Immunopharmacol., 2020, 80, 106179.
[http://dx.doi.org/10.1016/j.intimp.2019.106179] [PMID: 31972422]
[21]
Zheng, Y.; Ley, S.H.; Hu, F.B. Global aetiology and epidemiology of type 2 diabetes mellitus and its complications. Nat. Rev. Endocrinol., 2018, 14(2), 88-98.
[http://dx.doi.org/10.1038/nrendo.2017.151] [PMID: 29219149]
[22]
Zhao, T.; Yang, X.; Wan, R.; Yan, L.; Yang, R.; Guan, Y.; Wang, D.; Wang, H.; Wang, H. Study of TCM syndrome identification modes for patients with type 2 diabetes mellitus based on data mining. Evid. Based Complement. Alternat. Med., 2021, 2021, 5528550.
[http://dx.doi.org/10.1155/2021/5528550] [PMID: 34531918]
[23]
Xie, W.; Zhao, Y.; Zhang, Y. Traditional chinese medicines in treatment of patients with type 2 diabetes mellitus. Evid. Based Complement. Alternat. Med., 2011, 2011, 726723.
[http://dx.doi.org/10.1155/2011/726723] [PMID: 21584252]
[24]
Qi, L.W.; Wang, C.Z.; Yuan, C.S. Ginsenosides from American ginseng: Chemical and pharmacological diversity. Phytochemistry, 2011, 72(8), 689-699.
[http://dx.doi.org/10.1016/j.phytochem.2011.02.012] [PMID: 21396670]
[25]
Tanase, D.M.; Gosav, E.M.; Neculae, E.; Costea, C.F.; Ciocoiu, M.; Hurjui, L.L.; Tarniceriu, C.C.; Maranduca, M.A.; Lacatusu, C.M.; Floria, M.; Serban, I.L. Role of gut microbiota on onset and progression of microvascular complications of type 2 diabetes (T2DM). Nutrients, 2020, 12(12), 3719.
[http://dx.doi.org/10.3390/nu12123719] [PMID: 33276482]
[26]
Gomes, J.M.G.; Costa, J.A.; Alfenas, R.C.G. Metabolic endotoxemia and diabetes mellitus: A systematic review. Metabolism, 2017, 68, 133-144.
[http://dx.doi.org/10.1016/j.metabol.2016.12.009] [PMID: 28183445]
[27]
Jocken, J.W.E.; Goossens, G.H.; Boon, H.; Mason, R.R.; Essers, Y.; Havekes, B.; Watt, M.J.; van Loon, L.J.; Blaak, E.E. Insulin-mediated suppression of lipolysis in adipose tissue and skeletal muscle of obese type 2 diabetic men and men with normal glucose tolerance. Diabetologia, 2013, 56(10), 2255-2265.
[http://dx.doi.org/10.1007/s00125-013-2995-9] [PMID: 23907381]
[28]
Nowotny, B.; Zahiragic, L.; Krog, D.; Nowotny, P.J.; Herder, C.; Carstensen, M.; Yoshimura, T.; Szendroedi, J.; Phielix, E.; Schadewaldt, P.; Schloot, N.C.; Shulman, G.I.; Roden, M. Mechanisms underlying the onset of oral lipid-induced skeletal muscle insulin resistance in humans. Diabetes, 2013, 62(7), 2240-2248.
[http://dx.doi.org/10.2337/db12-1179] [PMID: 23454694]
[29]
Perreault, L.; Newsom, S.A.; Strauss, A.; Kerege, A.; Kahn, D.E.; Harrison, K.A.; Snell-Bergeon, J.K.; Nemkov, T.; D’Alessandro, A.; Jackman, M.R.; MacLean, P.S.; Bergman, B.C. Intracellular localization of diacylglycerols and sphingolipids influences insulin sensitivity and mitochondrial function in human skeletal muscle. JCI Insight, 2018, 3(3), e96805.
[http://dx.doi.org/10.1172/jci.insight.96805] [PMID: 29415895]
[30]
Calle, M.C.; Fernandez, M.L. Inflammation and type 2 diabetes. Diabetes Metab., 2012, 38(3), 183-191.
[http://dx.doi.org/10.1016/j.diabet.2011.11.006] [PMID: 22252015]
[31]
Peppa, M.; Stavroulakis, P.; Raptis, S.A. Advanced glycoxidation products and impaired diabetic wound healing. Wound Repair Regen., 2009, 17(4), 461-472.
[http://dx.doi.org/10.1111/j.1524-475X.2009.00518.x] [PMID: 19614910]
[32]
Akash, M.S.H.; Rehman, K.; Chen, S. Role of inflammatory mechanisms in pathogenesis of type 2 diabetes mellitus. J. Cell. Biochem., 2013, 114(3), 525-531.
[http://dx.doi.org/10.1002/jcb.24402] [PMID: 22991242]
[33]
Akash, M.S.H.; Rehman, K.; Liaqat, A. Tumor necrosis factor-alpha: Role in development of insulin resistance and pathogenesis of type 2 diabetes mellitus. J. Cell. Biochem., 2018, 119(1), 105-110.
[http://dx.doi.org/10.1002/jcb.26174] [PMID: 28569437]
[34]
Tan, K.C.B.; Chow, W.S.; Ai, V.H.G.; Metz, C.; Bucala, R.; Lam, K.S.L. Advanced glycation end products and endothelial dysfunction in type 2 diabetes. Diabetes Care, 2002, 25(6), 1055-1059.
[http://dx.doi.org/10.2337/diacare.25.6.1055] [PMID: 12032114]
[35]
Gao, X.; Zhang, H.; Schmidt, A.M.; Zhang, C. AGE/RAGE produces endothelial dysfunction in coronary arterioles in Type 2 diabetic mice. Am. J. Physiol. Heart Circ. Physiol., 2008, 295(2), H491-H498.
[http://dx.doi.org/10.1152/ajpheart.00464.2008] [PMID: 18539754]
[36]
Yamagishi, S.; Matsui, T.; Nakamura, K. Blockade of the advanced glycation end products (AGEs) and their receptor (RAGE) system is a possible mechanism for sustained beneficial effects of multifactorial intervention on mortality in type 2 diabetes. Med. Hypotheses, 2008, 71(5), 749-751.
[http://dx.doi.org/10.1016/j.mehy.2008.05.039] [PMID: 18710793]
[37]
Kay, A.M.; Simpson, C.L.; Stewart, J.A., Jr. The role of AGE/RAGE signaling in diabetes-mediated vascular calcification. J. Diabetes Res., 2016, 2016, 6809703.
[http://dx.doi.org/10.1155/2016/6809703] [PMID: 27547766]
[38]
Picchi, A.; Gao, X.; Belmadani, S.; Potter, B.J.; Focardi, M.; Chilian, W.M.; Zhang, C. Tumor necrosis factor-α induces endothelial dysfunction in the prediabetic metabolic syndrome. Circ. Res., 2006, 99(1), 69-77.
[http://dx.doi.org/10.1161/01.RES.0000229685.37402.80] [PMID: 16741160]
[39]
Gao, X.; Belmadani, S.; Picchi, A.; Xu, X.; Potter, B.J.; Tewari-Singh, N.; Capobianco, S.; Chilian, W.M.; Zhang, C. Tumor necrosis factor-α induces endothelial dysfunction in Lepr(db) mice. Circulation, 2007, 115(2), 245-254.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.106.650671] [PMID: 17200442]
[40]
Csiszar, A.; Ungvari, Z. Endothelial dysfunction and vascular inflammation in Type 2 diabetes: Interaction of AGE/RAGE and TNF-α signaling. Am. J. Physiol. Heart Circ. Physiol., 2008, 295(2), H475-H476.
[http://dx.doi.org/10.1152/ajpheart.00644.2008] [PMID: 18599592]
[41]
Anamthathmakula, P.; Winuthayanon, W. Prostaglandin-endoperoxide synthase 2 (PTGS2) in the oviduct: Roles in fertilization and early embryo development. Endocrinology, 2021, 162(4), bqab025.
[http://dx.doi.org/10.1210/endocr/bqab025] [PMID: 33539521]
[42]
Kunzmann, A.T.; Murray, L.J.; Cardwell, C.R.; McShane, C.M.; McMenamin, Ú.C.; Cantwell, M.M. PTGS2 (Cyclooxygenase-2) expression and survival among colorectal cancer patients: A systematic review. Cancer Epidemiol. Biomarkers Prev., 2013, 22(9), 1490-1497.
[http://dx.doi.org/10.1158/1055-9965.EPI-13-0263] [PMID: 23810915]
[43]
Cavelti-Weder, C.; Timper, K.; Seelig, E.; Keller, C.; Osranek, M.; Lässing, U.; Spohn, G.; Maurer, P.; Müller, P.; Jennings, G.T.; Willers, J.; Saudan, P.; Donath, M.Y.; Bachmann, M.F. Development of an interleukin-1β vaccine in patients with type 2 diabetes. Mol. Ther., 2016, 24(5), 1003-1012.
[http://dx.doi.org/10.1038/mt.2015.227] [PMID: 26686385]
[44]
Anquetil, F.; Sabouri, S.; Thivolet, C.; Rodriguez-Calvo, T.; Zapardiel-Gonzalo, J.; Amirian, N.; Schneider, D.; Castillo, E.; Lajevardi, Y.; von Herrath, M.G. Alpha cells, the main source of IL-1β in human pancreas. J. Autoimmun., 2017, 81, 68-73.
[http://dx.doi.org/10.1016/j.jaut.2017.03.006] [PMID: 28325643]
[45]
Wang, G.; Liang, R.; Liu, T.; Wang, L.; Zou, J.; Liu, N.; Liu, Y.; Cai, X.; Liu, Y.; Ding, X.; Zhang, B.; Wang, Z.; Wang, S.; Shen, Z. Opposing effects of IL-1β/COX-2/PGE2 pathway loop on islets in type 2 diabetes mellitus. Endocr. J., 2019, 66(8), 691-699.
[http://dx.doi.org/10.1507/endocrj.EJ19-0015] [PMID: 31105125]
[46]
Tran, P.O.T.; Gleason, C.E.; Robertson, R.P. Inhibition of interleukin-1β-induced COX-2 and EP3 gene expression by sodium salicylate enhances pancreatic islet β-cell function. Diabetes, 2002, 51(6), 1772-1778.
[http://dx.doi.org/10.2337/diabetes.51.6.1772] [PMID: 12031964]
[47]
Wu, Q.; Chen, X.; He, Q.; Lang, L.; Xu, P.; Wang, P.; Lee, S.C. Resveratrol attenuates diabetes-associated cell centrosome amplification via inhibiting the PKCα-p38 to c-myc/c-jun pathway. Acta Biochim. Biophys. Sin., 2019, 52(1), 72-83.
[http://dx.doi.org/10.1093/abbs/gmz142] [PMID: 31844893]
[48]
Nakashima, S. Protein kinase C α (PKC α): Regulation and biological function. J. Biochem., 2002, 132(5), 669-675.
[http://dx.doi.org/10.1093/oxfordjournals.jbchem.a003272] [PMID: 12417014]
[49]
Miele, C.; Paturzo, F.; Teperino, R.; Sakane, F.; Fiory, F.; Oriente, F.; Ungaro, P.; Valentino, R.; Beguinot, F.; Formisano, P. Glucose regulates diacylglycerol intracellular levels and protein kinase C activity by modulating diacylglycerol kinase subcellular localization. J. Biol. Chem., 2007, 282(44), 31835-31843.
[http://dx.doi.org/10.1074/jbc.M702481200] [PMID: 17675299]
[50]
Wang, M.; Zhong, H.; Zhang, X.; Huang, X.; Wang, J.; Li, Z.; Chen, M.; Xiao, Z. EGCG promotes PRKCA expression to alleviate LPS-induced acute lung injury and inflammatory response. Sci. Rep., 2021, 11(1), 11014.
[http://dx.doi.org/10.1038/s41598-021-90398-x] [PMID: 34040072]
[51]
Morrison, M.C.; Kleemann, R. Role of macrophage migration inhibitory factor in obesity, insulin resistance, type 2 diabetes, and associated hepatic co-morbidities: A comprehensive review of human and rodent studies. Front. Immunol., 2015, 6, 308.
[http://dx.doi.org/10.3389/fimmu.2015.00308] [PMID: 26124760]
[52]
Morrison, M.C.; Kleemann, R.; van Koppen, A.; Hanemaaijer, R.; Verschuren, L. Key inflammatory processes in human NASH are reflected in Ldlr−/−. Leiden mice: A translational gene profiling study. Front. Physiol., 2018, 9, 132.
[http://dx.doi.org/10.3389/fphys.2018.00132] [PMID: 29527177]
[53]
Ghanooni, R.; Decaestecker, C.; Simon, P.; Gabius, H.J.; Hassid, S.; Choufani, G. Characterization of patterns of expression of protein kinase C-α, -δ, -η, -γ and -ζ and their correlations to p53, galectin-3, the retinoic acid receptor-β and the macrophage migration inhibitory factor (MIF) in human cholesteatomas. Hear. Res., 2006, 214(1-2), 7-16.
[http://dx.doi.org/10.1016/j.heares.2006.01.013] [PMID: 16513304]
[54]
Li, L.; Zhang, Z.T. Genetic association between NFKBIA and NFKB1 gene polymorphisms and the susceptibility to head and neck cancer: A meta-analysis. Dis. Markers, 2019, 2019, 1-10.
[http://dx.doi.org/10.1155/2019/6523837] [PMID: 31612070]
[55]
Chen, M.; Liang, X.; Liang, Z.; Zhao, L. Study on the effect and mechanism of NFKBIA on cervical cancer progress in vitro and in vivo. J. Obstet. Gynaecol. Res., 2021, 47(11), 3931-3942.
[http://dx.doi.org/10.1111/jog.14947] [PMID: 34342105]
[56]
Itani, S.I.; Ruderman, N.B.; Schmieder, F.; Boden, G. Lipid-induced insulin resistance in human muscle is associated with changes in diacylglycerol, protein kinase C, and IkappaB-α. Diabetes, 2002, 51(7), 2005-2011.
[http://dx.doi.org/10.2337/diabetes.51.7.2005] [PMID: 12086926]
[57]
Arkan, M.C.; Hevener, A.L.; Greten, F.R.; Maeda, S.; Li, Z.W.; Long, J.M.; Wynshaw-Boris, A.; Poli, G.; Olefsky, J.; Karin, M. IKK-β links inflammation to obesity-induced insulin resistance. Nat. Med., 2005, 11(2), 191-198.
[http://dx.doi.org/10.1038/nm1185] [PMID: 15685170]
[58]
Cai, D.; Yuan, M.; Frantz, D.F.; Melendez, P.A.; Hansen, L.; Lee, J.; Shoelson, S.E. Local and systemic insulin resistance resulting from hepatic activation of IKK-β and NF-κB. Nat. Med., 2005, 11(2), 183-190.
[http://dx.doi.org/10.1038/nm1166] [PMID: 15685173]
[59]
Fettke, H.; Kwan, E.M.; Bukczynska, P.; Steen, J.A.; Docanto, M.; Ng, N.; Parente, P.; Mant, A.; Foroughi, S.; Pezaro, C.; Hauser, C.; Nguyen-Dumont, T.; Southey, M.C.; Azad, A.A. Independent prognostic impact of plasma NCOA2 alterations in metastatic castration‐resistant prostate cancer. Prostate, 2021, 81(13), 992-1001.
[http://dx.doi.org/10.1002/pros.24194] [PMID: 34254334]
[60]
Picard, F.; Géhin, M.; Annicotte, J.S.; Rocchi, S.; Champy, M.F.; O’Malley, B.W.; Chambon, P.; Auwerx, J. SRC-1 and TIF2 control energy balance between white and brown adipose tissues. Cell, 2002, 111(7), 931-941.
[http://dx.doi.org/10.1016/S0092-8674(02)01169-8] [PMID: 12507421]
[61]
Choi, C.S.; Befroy, D.E.; Codella, R.; Kim, S.; Reznick, R.M.; Hwang, Y.J.; Liu, Z.X.; Lee, H.Y.; Distefano, A.; Samuel, V.T.; Zhang, D.; Cline, G.W.; Handschin, C.; Lin, J.; Petersen, K.F.; Spiegelman, B.M.; Shulman, G.I. Paradoxical effects of increased expression of PGC-1α on muscle mitochondrial function and insulin-stimulated muscle glucose metabolism. Proc. Natl. Acad. Sci. USA, 2008, 105(50), 19926-19931.
[http://dx.doi.org/10.1073/pnas.0810339105] [PMID: 19066218]
[62]
Duteil, D.; Chambon, C.; Ali, F.; Malivindi, R.; Zoll, J.; Kato, S.; Geny, B.; Chambon, P.; Metzger, D. The transcriptional coregulators TIF2 and SRC-1 regulate energy homeostasis by modulating mitochondrial respiration in skeletal muscles. Cell Metab., 2010, 12(5), 496-508.
[http://dx.doi.org/10.1016/j.cmet.2010.09.016] [PMID: 21035760]
[63]
Radha, V.; Vimaleswaran, K.S.; Ayyappa, K.A.; Mohan, V. Association of lipoprotein lipase gene polymorphisms with obesity and type 2 diabetes in an Asian Indian population. Int. J. Obes., 2007, 31(6), 913-918.
[http://dx.doi.org/10.1038/sj.ijo.0803547] [PMID: 17299379]
[64]
Martínez-Ramírez, O.C.; Salazar-Piña, D.A.; de Lorena, R.G.M.; Castro-Hernández, C.; Casas-Ávila, L.; Portillo-Jacobo, J.A.; Rubio, J. Association of NFκβ, TNFα, IL-6, IL-1β, and LPL Polymorphisms with Type 2 Diabetes Mellitus and Biochemical Parameters in a Mexican Population. Biochem. Genet., 2021, 59(4), 940-965.
[http://dx.doi.org/10.1007/s10528-021-10047-w] [PMID: 33599871]
[65]
Cho, Y.S.; Go, M.J.; Han, H.R.; Cha, S.H.; Kim, H.T.; Min, H.; Shin, H.D.; Park, C.; Han, B.G.; Cho, N.H.; Shin, C.; Kimm, K.; Oh, B. Association of lipoprotein lipase (LPL) single nucleotide polymorphisms with type 2 diabetes mellitus. Exp. Mol. Med., 2008, 40(5), 523-532.
[http://dx.doi.org/10.3858/emm.2008.40.5.523] [PMID: 18985010]

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